Zero dose extrapolation

Features and Functionality
1

Hi CryoSPARC community, I haven’t used CryoSPARC in a while, just wondering if zero-dose extrapolation is now available in the latest release?

2

Hi @Mayin,

Thanks for your inquiry! Currently, we do not offer an option for 0-dose extrapolation during reconstruction. It is worth noting however that radiation damage is accounted for during dose weighting through use of a standard dose weight curve (in e.g., Patch Motion) or an empirically derived dose weight curve if Reference-based Motion Correction is performed.

We have a few follow up questions regarding your use case below:

  1. Do you currently have a use case where you believe 0-dose extrapolated reconstructions would be beneficial?

  2. Are you already using HexAuFoil grids for your projects?

Best,
Kye

3

Hi Crysosparc team, @kstachowski

I would second the question/request for zero-dose extrapolation in cryosparc. I did attempt using HexAuFoil grids and they worked in principle, but on their own they don’t seem to offer enough benefits to be worth switching to. I routinely work with reconstructions in 2.2-2.5 A range for small-molecule- protein complexes and at these resolution radiation damage is quite apparent, to both protein and small-molecules. I could imagine a scenario where removing or at least reducing radiation damage could influence the data in a major way, especially if relevant binding sites are contain carboxylates or disulfides.

4

Hi @kstachowski Kye!

There are many of us working with proteins containing metal centers for which doing 0-dose extrapolation is very important. Of course, the use of HeaxaFoil grids for that purpose is advised. If you can speed up such implementation, I am sure many of us would benefit. Note that this feauture has been requested and discussed in other topics in the forum such as in here https://discuss.cryosparc.com/t/reconstructions-with-subsets-of-frames/7456/9

It would be nice if you could bump this request as a priority in CS roadmap.

Thank you,

André

5

Hi @maraam07 and @AndreGraca,

Thanks for your feedback, especially related to metalloproteins and specific ligand in which this might be useful. This request and your feedback has been noted.

Best,

Kye

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